This invention is concerned with a process for dehydrogenating azasteroids, in particular 17.beta. substituted 3-oxo-4 azasteroids, to provide the corresponding compound having a double bond at its 1,2 position.
Heretofore, azasteroids have been dehydrogenated to introduce a 1,2 double bond by means of benzene seleninic anhydride oxidation in which the saturated compound was heated with the benzene seleninic anhydride in refluxing chlorobenzene. Back, T. G., J. Org. Chem., 46, 1442 (1981); Rasmussen et al., J. Med. Chem. 29, 2298 (1986), Dehydrogenation of azasteroids utilizing benzeneseleninic acid or benzene seleninic anhydride to form the corresponding .DELTA..sup.1 compound is also discussed in Back, T. G., J.C.S. Chem. Comm., 278-279 (1978). Additionally, sulfoxide elimination has been a process used to accomplish the dehydrogenation. See U.S. Pat. Nos. 4,377,584, 4,220,775 and EP application 85301122.9. However these reactions have been found to give poor yields, with a high degree of impurities and one requires the use of a selenium catalyst which is very expensive and is quite toxic.
It has also been known to dehydrogenate a 3-oxo-4-azalactam by a complicated 5-step process which involves a sulfenate intermediate. See Magnus et al., J. Am. Chem., 108, 221-227 (1986). More recently, a dehydrogenation process involving a silylation-mediated DDQ oxidation of 4-aza-3-ketosteroids to the corresponding .DELTA..sup.1 -lactams has been
developed. See Bhattacharya et al., J. Am. Chem. Soc., 110, 3318 (1988).
The process of the present invention provides a method for introducing a 1,2 double bond into 17.beta.-substituted 3-oxo-4 azasteroids via a four step process utilizing oxalyl chloride. The present invention provides a method to dehydrogenate a wide variety of compounds while avoiding the disadvantages of the prior art methods. These disadvantages include poor yields, expensive reagents, unwanted by-products and the use of toxic selenium catalysts.